Is MPEG1 p.Pro635= (c.1905G>T) pathogenic?

MPEG1 p.Pro635= (c.1905G>T) is classified Likely benign in MPEG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-01). Rare (popmax 0.85%, nfe).

How common is MPEG1 p.Pro635= (c.1905G>T) in the general population?

MPEG1 p.Pro635= (c.1905G>T) is rare (popmax 0.85%, nfe) (gnomAD).

MPEG1 p.Pro635=

c.1905G>T · VCV3770442

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.85%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -3.4
Overall
CADD	0.049	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.85% European (non-Finnish) · 10,034/1,180,034 alleles

Filtering AF 0.836% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.831%

Overall 0.705% 11,373/1,614,196 alleles · rare exomes 10,640/1,461,892 · genomes 733/152,304 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.08%	93
European (non-Finnish)grpmax	0.85%	118
Remaining individualsnot grpmax-eligible	0.517%	194
Admixed American	0.14%	715
South Asian	0.122%	821
African / African-American	0.12%	834
Ashkenazi Jewishnot grpmax-eligible	0.115%	871
Middle Eastern	0.099%	1,010
East Asian	0.00446%	22,443

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MPEG1
Protein: p.Pro635=
Coding: c.1905G>T
MANE Select: NM_001039396
Type: single nucleotide variant
Location: chr11:59210961 (GRCh38)
Gene constraint: LOEUF 1.941 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 83.22 · 5 PDB
Residue 635: a UniProt-annotated variant site (in imd77; decreased defense response to bacterium); the 'p2' region; an α-helix

Full MPEG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MPEG1 p.Pro635Leu Uncertain significance ★ ⚠ same residue
MPEG1 p.Ala525Val Uncertain significance ★★ ⚠ same type
MPEG1 p.Gln259Glu Uncertain significance ★★ ⚠ same type
MPEG1 p.Gln713Arg Uncertain significance ★★ ⚠ same type
MPEG1 p.His420Tyr Uncertain significance ★★ ⚠ same type
MPEG1 p.Ala467= Benign ★★ same type
MPEG1 p.Thr73Ala Likely benign ★★ same type
MPEG1 p.Ala238Thr Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mpeg1-p-pro635 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown